Is LEMD3 p.Ser402Phe (c.1205C>T) pathogenic?

LEMD3 p.Ser402Phe (c.1205C>T) is classified Benign/Likely benign in LEMD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.1205); Very rare (popmax 0.01%, amr); Associated with Buschke-Ollendorff syndrome.

What condition is associated with LEMD3 p.Ser402Phe (c.1205C>T)?

LEMD3 p.Ser402Phe (c.1205C>T) is associated with Buschke-Ollendorff syndrome (ClinVar).

How common is LEMD3 p.Ser402Phe (c.1205C>T) in the general population?

LEMD3 p.Ser402Phe (c.1205C>T) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about LEMD3 p.Ser402Phe (c.1205C>T)?

AlphaMissense predicts likely benign (score 0.1205) — an in-silico prediction, not a clinical call.

LEMD3 p.Ser402Phe

c.1205C>T · rs139346096 · VCV883454

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1205 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Buschke-Ollendorff syndrome

Computational evidence

Protein change
AlphaMissense	0.1205	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -9.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 0.99
Regional constraint	o/e 1.20	unconstrained · MANE · 1,339 bp · p 4.4e-07 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,010 alleles

Filtering AF 0.00681% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.0273% 441/1,614,014 alleles · very rare exomes 399/1,461,890 · genomes 42/152,124 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.946%	106
Remaining individualsnot grpmax-eligible	0.0832%	1,202
Admixed Americangrpmax	0.01%	10,002
European (non-Finnish)	0.00814%	12,292
African / African-American	0.00401%	24,963
South Asian	0.00329%	30,359
East Asian	0.00223%	44,884

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: LEMD3
Protein: p.Ser402Phe
Coding: c.1205C>T
MANE Select: NM_014319
dbSNP: rs139346096
Type: single nucleotide variant
Location: chr12:65170801 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI 0.40 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.07 · 3 PDB
Residue 402: a modified residue (phosphoserine)

Full LEMD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Buschke-Ollendorff syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LEMD3 p.Ser402Cys Uncertain significance ★ ⚠ same residue
LEMD3 p.Arg678Ter Pathogenic/Likely pathogenic ★★ same condition
LEMD3 p.Glu601Ter Pathogenic/Likely pathogenic ★★ same condition
LEMD3 p.Ala127Val Uncertain significance ★★ ⚠ same condition
LEMD3 p.Asn257Asp Uncertain significance ★★ ⚠ same condition
LEMD3 p.Asn529Ser Uncertain significance ★★ ⚠ same condition
LEMD3 p.Asp214Tyr Uncertain significance ★★ ⚠ same condition
LEMD3 p.Asp544Ala Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/lemd3-p-ser402phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown